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Creators/Authors contains: "Becker, Danielle M."

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  1. Abstract

    Genetic mutations to the Lamin A/C gene (LMNA) can cause heart disease, but the mechanisms making cardiac tissues uniquely vulnerable to the mutations remain largely unknown. Further, patients withLMNAmutations have highly variable presentation of heart disease progression and type.In vitropatient-specific experiments could provide a powerful platform for studying this phenomenon, but the use of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) introduces heterogeneity in maturity and function thus complicating the interpretation of the results of any single experiment. We hypothesized that integrating single cell RNA sequencing (scRNA-seq) with analysis of the tissue architecture and contractile function would elucidate some ofmore »the probable mechanisms. To test this, we investigated five iPSC-CM lines, three controls and two patients with a (c.357-2A>G) mutation. The patient iPSC-CM tissues had significantly weaker stress generation potential than control iPSC-CM tissues demonstrating the viability of ourin vitroapproach. Through scRNA-seq, differentially expressed genes between control and patient lines were identified. Some of these genes, linked to quantitative structural and functional changes, were cardiac specific, explaining the targeted nature of the disease progression seen in patients. The results of this work demonstrate the utility of combiningin vitrotools in exploring heart disease mechanics.

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  2. Coral reefs, one of the most diverse ecosystems in the world, face increasing pressures from global and local anthropogenic stressors. Therefore, a better understanding of the ecological ramifications of warming and land-based inputs (e.g., sedimentation and nutrient loading) on coral reef ecosystems is necessary. In this study, we measured how a natural nutrient and sedimentation gradient affected multiple facets of coral functionality, including endosymbiont and coral host response variables, holobiont metabolic responses, and percent cover of Pocillopora acuta colonies in Mo'orea, French Polynesia. We used thermal performance curves to quantify the relationship between metabolic rates and temperature along the environmentalmore »gradient. We found that algal endosymbiont % nitrogen content, endosymbiont densities, and total chlorophyll a content increased with nutrient input, while endosymbiont nitrogen content cell−1 decreased, likely representing competition among the algal endosymbionts. Nutrient and sediment loading decreased coral metabolic responses to thermal stress in terms of their thermal performance and metabolic rate processes. The acute thermal optimum for dark respiration decreased, along with the maximal performance for gross photosynthetic and calcification rates. Gross photosynthetic and calcification rates normalized to a reference temperature (26.8 °C) decreased along the gradient. Lastly, percent cover of P. acuta colonies decreased by nearly two orders of magnitude along the nutrient gradient. These findings illustrate that nutrient and sediment loading affect multiple levels of coral functionality. Understanding how local-scale anthropogenic stressors influence the responses of corals to temperature can inform coral reef management, particularly on the mediation of land-based inputs into coastal coral reef ecosystems.« less
  3. null (Ed.)